What is the Endocannabinoid System?
The Endocannabinoid System (ECS) is a regulatory system found in all vertebrate species, including humans. This system, and the natural cannabinoids produced by the body that interact with the ECS serve to maintain homeostasis (Cottone 2013). This means that it sends feedback signals to cells to make sure their function is balanced, and not overactive or stagnant. Nature, a high profile nature-based research journal, published cannabis studies with THC in 1988 that led to the discovery of this system (Marzo 2004). The cannabinoids found in the cannabis plant interact with ECS receptors in our bodies to produce their characteristic effects.
THE ENDOCANNABINOID SYSTEM IN CELL RECEPTORS
The ECS is governed by two types of cell receptors, CB1 and CB2. These receptors are found on the surface of cells throughout the body, the highest concentrations of which are located in the cells of the brain and nervous system. CB1 is much more concentrated in the brain and spinal cord while CB2 is mostly found in cells associated with the immune system (Pagotto 2006). Two cannabinoids are naturally produced by the human body, and are the signaling molecules which bind to these receptors to carry out their function. These internally produced (endogenous) molecules have been identified as Anandamide and 2-AG. Once they have performed their function, they are broken down by enzymes. The ECS in our body that is made up of these receptors naturally produces these cannabinoids and enzymes which help regulate a variety of systems in our body. These systems may include but are not limited to pain, appetite, and reproduction.
The high concentration of CB1 in the brain and nervous system is due to its close association with neurotransmitter release and regulation (Marzo 1998). High concentrations of these receptors are found at the synapses between neurons. Neurotransmitters are chemicals in the body, such as dopamine and serotonin, that act as signals between neurons. When you feel pain, neurons release neurotransmitters from neuron to neuron through synapses in order to communicate to the brain that something is painful. If these neurons malfunction and keep sending signals over and over, the pain felt would be unbearable. That’s where the ECS comes in. Endocannabinoids are able to calm overactive neurons and return them to a baseline state of function. This occurs in the reverse as well. Neuron cells that are inactive can be triggered to activate by the ECS (Sulak 2018
HOW THE ENDOCANNABINOID SYSTEM MAY AFFECT DISORDERS AND HORMONES
The ECS is also involved in brain functions relating to seizures when the cells in the brain are not communicating and functioning normally (Marzo 2004). The FDA approved Epidiolex for the treatment of seizures in pediatric patients. The active ingredient is CBD, which interacts with the ECS to regulate brain signaling and lessen the occurrence of seizures. The ECS plays a large role in the regulation of this communication and therefore is often targeted by medication to mitigate these problems. It also plays a role in the endocrine system which regulates the release and uptake of hormones. The pituitary gland, which is directly attached to the brain, secretes hormones throughout the body to signal everything from hunger to the fight or flight response, and has many endocannabinoid receptors (Pagotto 2006). The list of functions in the body associated with the ECS is extremely long, but in all cases, it serves to keep cells functioning normally in homeostasis.
THE EFFECTS OF CANNABIS & CBD ON THE ENDOCANNABINOID SYSTEM
Cannabis and its cannabinoids have been used for centuries in order to interact with this complex system in our body. In fact, the reason we know about the ECS is because cannabis has been widely used throughout history and scientists wanted to know how it functioned in our body (Marzo 2004). Like the endogenous cannabinoids already present in our bodies, THC and CBD are able to interact with the ECS receptors to produce their desired effects. The reason cannabinoids are being touted to the pharmaceutical industry is due to the fact that we have receptors for these molecules all over our body. THC binds strongly to CB1 receptors. Because there is such a high concentration of CB1 in the brain, people get the psychoactive effects that THC is known for. The reason this psychoactivity doesn’t last forever is because humans already have the enzymes necessary to break down cannabinoids. CBD also interacts with these receptors, although studies have shown that it can actually block CB1 receptors, lessening the undesirable or psychoactive effects of THC (McPartland 2014). Cannabis’ famous effect on the appetite can also be linked to the presence of ECS receptors in the GI tract and the pituitary gland.
The Endocannabinoid System is very complex and keeps our cells and associated systems in check. Maintaining a homeostatic balance is essential for survival. Because the ECS is so widespread in the body and performs regulatory functions, it is a good system to target with prescription drugs such as Epidolex and others that are FDA approved which are modeled after cannabinoids. There is a lot of ongoing research about the precise function of cannabinoids and how they interact with receptors. Scientists are trying to figure out the specific functionality and pathways of these molecules in the ECS in order to develop pharmaceuticals. Of the top 150 pharmaceuticals in the US, 118 are plant-derived (Roberson 2008). With over 80 unique cannabinoids, cannabis has huge potential for a diverse range of interactions with the ECS and scientists and researchers are racing to find out exactly how they function and if they could serve as components of medicine in the future.